Synthesis and hybridization properties of the conjugates of oligonucleotides and stabilization agents. Part 3 Original Research Article

New compounds having tri- or pentamethylenamine linker functions were synthesized. These derivatives were covalently attached through the 5′-phosphoramide linkage to heptanucleotide pd(CCAAACA). Complementary complexes of the octanucleotide pd(TGTTTGGC) and above oligonucleotide conjugates were tested for their thermodynamic response. The Tm data and thermodynamic parameters for complex formation confirmed the ability of chromone (γ-pyrone) derivatives to stabilize strongly the 7-mer/8-mer complementary complex. Moreover, benzochromone (naphthopyrane) and, surprisingly, tetrahydropyrimidinethanone derivatives showed the capacity of stabilizing this 7-mer/8-mer complementary complex. The effect of all these compounds on the stability of the oligonucleotide complexes (ΔΔG at 37 °C ranged from −1.2 to −2.0 kcal/mol) was shown to be comparable to the effect of one nucleotide base pair and similar to the effect (ΔΔG at 37 °C ranged from −1.5 to −2.0 kcal/mol) found for acridine–oligonucleotide conjugates, which served as a reference in this study.